{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:08:47Z","timestamp":1789697327921,"version":"4.0.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["413657723"],"award-info":[{"award-number":["413657723"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fluid overload (FO) is an established risk factor for mortality in hemodialysis patients, who face higher cardiovascular mortality risk than the general population. Despite the known impact of FO on cardiovascular outcomes, the effects of cumulative FO exposure, dialysate sodium \u2264138\u00a0mmol\/l, and specific cardiac deaths remain unclear. This study aimed to assess these relationships in a large cohort of hemodialysis patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This historical cohort study included 68\u2009196 hemodialysis patients from the NephroCare network with data from 2010 to 2019. Eligible patients had valid bioimpedance, plasma, and dialysate sodium measurements within 90 days of starting hemodialysis. FO was defined as &amp;gt;7% relative FO, as assessed by bioimpedance spectroscopy. Cause-specific Cox proportional hazards models were used to evaluate the impact of these exposures on different cardiac endpoints, including death from heart failure, sudden cardiac death, and fatal myocardial infarction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 68\u2009196 patients, a total of 2\u2009123\u2009957 patient-months were analyzed. Compared to patients with no prior exposure (0 month cumulative past exposure time), increasing cumulative exposure to FO (measured in months) significantly increased the risk of death from heart failure [hazard ratio (HR) peaking at 4.4, 95%CI: 3.4\u20135.6], sudden cardiac death (HR peaking at 4.0, 95%CI: 3.1\u20135.2), and fatal myocardial infarction (HR peaking at 3.3, 95%CI: 2.5\u20134.4). Cumulative exposure (in month) to dialysate sodium \u2264138\u00a0mmol\/l was associated with an elevated risk of death from heart failure (HR peaking at 6.0, 95%CI: 1.9\u201318.3) and a moderate increase in sudden cardiac death (HR peaking at 2.7, 95%CI: 1.3\u20135.6). The risk of all-cause mortality was consistently higher in patients exposed to FO (HR peaking at 3.4, 95%CI: 3.1\u20133.8) and those exposed to dialysate sodium \u2264138\u00a0mmol\/l (HR peaking at 2.0, 95%CI: 1.3\u20133.1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cumulative FO and dialysate sodium \u2264138\u00a0mmol\/l significantly increase cardiac death risk in hemodialysis patients, particularly from heart failure. Stringent fluid management and careful consideration of dialysate sodium prescription is crucial to reduce cardiovascular mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfaf259","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T11:22:57Z","timestamp":1755516177000},"source":"Crossref","is-referenced-by-count":3,"title":["Increased risk of cardiac death with cumulative exposure to fluid overload and dialysate sodium \u2264138\u00a0mmol\/l in hemodialysis patients"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8703-7644","authenticated-orcid":false,"given":"Martin","family":"Christa","sequence":"first","affiliation":[{"name":"University Hospital W\u00fcrzburg Department for interal Medicine, , W\u00fcrzburg,","place":["Germany"]},{"name":"Hospital Northwest Heart-Lung Center, Department for Internal Medicine, , Frankfurt am Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1838-3348","authenticated-orcid":false,"given":"Brendan","family":"Smyth","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre, University of Sydney , Camperdown, NSW ,","place":["Australia"]},{"name":"St George Hospital Department of Renal Medicine, , Kogarah, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5695-0270","authenticated-orcid":false,"given":"Kaitlin J","family":"Mayne","sequence":"additional","affiliation":[{"name":"University of Glasgow , Glasgow,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-4507","authenticated-orcid":false,"given":"Stefano","family":"Stuard","sequence":"additional","affiliation":[{"name":"Global Medical Office, FMC Germany , Bad Homburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-2816","authenticated-orcid":false,"given":"Bernard","family":"Canaud","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre, University of Sydney , Camperdown, NSW ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Genser","sequence":"additional","affiliation":[{"name":"University Hospital W\u00fcrzburg Department for interal Medicine, , W\u00fcrzburg,","place":["Germany"]},{"name":"High5Data GmbH , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jule","family":"Pinter","sequence":"additional","affiliation":[{"name":"University Hospital W\u00fcrzburg Department for interal Medicine, , W\u00fcrzburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"2025102205420115400_bib1","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1681\/ASN.2016121341","article-title":"Chronic fluid overload and mortality in ESRD","volume":"28","author":"Zoccali","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"2025102205420115400_bib2","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.2215\/CJN.0000000000000552","article-title":"Associations of abnormal fluid status, plasma sodium disorders, and low dialysate sodium with mortality in patients on hemodialysis","volume":"19","author":"Pinter","year":"2024","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025102205420115400_bib3","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1681\/ASN.0000000000000299","article-title":"Update on hemodialysis-induced multiorgan ischemia: brains and beyond","volume":"35","author":"McIntyre","year":"2024","journal-title":"J Am Soc Nephrol"},{"key":"2025102205420115400_bib4","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1001\/jama.2009.1488","article-title":"Cardiovascular and noncardiovascular mortality among patients starting dialysis","volume":"302","author":"De Jager","year":"2009","journal-title":"JAMA"},{"key":"2025102205420115400_bib5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1681\/ASN.0000000000000262","article-title":"Effect of dialysate and plasma sodium on mortality in a global historical hemodialysis cohort","volume":"35","author":"Pinter","year":"2024","journal-title":"J Am Soc Nephrol"},{"key":"2025102205420115400_bib6","first-page":"CD011204","article-title":"Low dialysate sodium levels for chronic haemodialysis","author":"Dunlop","year":"2019","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"2025102205420115400_bib7","doi-asserted-by":"publisher","first-page":"92","DOI":"10.2215\/CJN.05440611","article-title":"Dialysate sodium concentration and the association with interdialytic weight gain, hospitalization, and mortality","volume":"7","author":"Hecking","year":"2012","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025102205420115400_bib8","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1053\/j.ajkd.2015.07.015","article-title":"KDOQI Clinical Practice Guideline for Hemodialysis adequacy: 2015 update","volume":"66","author":"Daugirdas","year":"2015","journal-title":"Am J Kidney Dis"},{"key":"2025102205420115400_bib9","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1088\/0967-3334\/27\/9\/012","article-title":"Body fluid volume determination via body composition spectroscopy in health and disease","volume":"27","author":"Moissl","year":"2006","journal-title":"Physiol Meas"},{"key":"2025102205420115400_bib10","doi-asserted-by":"publisher","first-page":"e001918","DOI":"10.1161\/JAHA.115.001918","article-title":"Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies","volume":"4","author":"Hung","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"2025102205420115400_bib11","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1093\/ajcn\/85.1.80","article-title":"A whole-body model to distinguish excess fluid from the hydration of major body tissues","volume":"85","author":"Chamney","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"2025102205420115400_bib12","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1093\/ndt\/gfn707","article-title":"The mortality risk of overhydration in haemodialysis patients","volume":"24","author":"Wizemann","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"2025102205420115400_bib13","doi-asserted-by":"publisher","first-page":"e0183281","DOI":"10.1371\/journal.pone.0183281","article-title":"Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease","volume":"12","author":"Mitsides","year":"2017","journal-title":"PLoS ONE"},{"key":"2025102205420115400_bib14","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1093\/ndt\/gfad041","article-title":"Hyponatraemia and fluid overload are associated with higher risk of mortality in dialysis patients","volume":"38","author":"Pinter","year":"2023","journal-title":"Nephrol Dial Transplant"},{"key":"2025102205420115400_bib15","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12940-015-0047-2","article-title":"Within- and between-group regression for improving the robustness of causal claims in cross-sectional analysis","volume":"14","author":"Genser","year":"2015","journal-title":"Environ Health"},{"key":"2025102205420115400_bib16","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/S0140-6736(16)30508-6","article-title":"The heart and vascular system in dialysis","volume":"388","author":"Wanner","year":"2016","journal-title":"Lancet"},{"key":"2025102205420115400_bib17","doi-asserted-by":"publisher","first-page":"ii23","DOI":"10.1093\/ndt\/gfaa017","article-title":"Sodium, volume and pressure control in haemodialysis patients for improved cardiovascular outcomes","volume":"35","author":"Pinter","year":"2020","journal-title":"Nephrol Dial Transplant"},{"key":"2025102205420115400_bib18","doi-asserted-by":"publisher","first-page":"790","DOI":"10.2215\/CJN.05921108","article-title":"Pediatric myocardial stunning underscores the cardiac toxicity of conventional hemodialysis treatments","volume":"4","author":"Hothi","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025102205420115400_bib19","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1093\/ndt\/gfn501","article-title":"Haemodialysis is associated with a pronounced fall in myocardial perfusion","volume":"24","author":"Dasselaar","year":"2008","journal-title":"Nephrol Dial Transplant"},{"key":"2025102205420115400_bib20","doi-asserted-by":"publisher","first-page":"914","DOI":"10.2215\/CJN.03900808","article-title":"Hemodialysis-induced cardiac injury: determinants and associated outcomes","volume":"4","author":"Burton","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025102205420115400_bib21","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/sdi.12197","article-title":"Hemodialysis-associated cardiomyopathy: a newly defined disease entity","volume":"27","author":"McIntyre","year":"2014","journal-title":"Semin Dial"},{"key":"2025102205420115400_bib22","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1159\/000487702","article-title":"Effects of volume overload and current techniques for the assessment of fluid status in patients with renal disease","volume":"46","author":"Ekinci","year":"2018","journal-title":"Blood Purif"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfaf259\/64083991\/sfaf259.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/18\/10\/sfaf259\/64083991\/sfaf259.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/18\/10\/sfaf259\/64083991\/sfaf259.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T09:42:07Z","timestamp":1761126127000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/doi\/10.1093\/ckj\/sfaf259\/8238076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":22,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,3]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfaf259","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,8,19]]},"article-number":"sfaf259"}}